Obama Signs Memo to 'Protect' Science & Funding for Stem Cell Research

At the White House signing this afternoon of an executive order to overturn the previous administration's ban on using human embryonic stem cells in research, US President Barack Obama also signed a memorandum that he said is aimed at insulating science from politics.

Obama said today that the Scientific Integrity Presidential Memorandum charges the White House Office of Science and Technology Policy with development of "a strategy for restoring scientific integrity to government decision making." He said that his administration will "base our public policies on the soundest science …[and] appoint scientific advisors based on their credentials and experience, not their politics or ideology." In addition, Obama said that his administration will be "open and honest with the American people about the science behind our decisions."

He also said that promoting science is about more than providing resources, but also involves "ensuring that scientific data is never distorted or concealed to serve a political agenda – and that we make scientific decisions base on facts, not ideology." The memorandum gives the director 120 days to develop a set of recommendations based on several principles, including those pertaining to: how candidates are hired; how integrity is protected within agencies; how information used in making policy decisions is reviewed; how agencies shall make scientific and technical knowledge public, when possible; and how whistleblower and other protections should be adopted for protecting the integrity of research.

It also states that the heads of the different research agencies will work with the OSTP director to develop recommendations for the White House.

President Barack Obama’s Executive Order to allow the National Institutes of Health (NIH) to fund research using embryonic stem cells.


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New Drug Reverses Alzheimer's Disease Within Day

Scientists report a remarkable improvement in Alzheimer's transgenic mice following treatment with a new drug. The study provides the first demonstration that an ionophore, a compound that transports metal ions across cell membranes, can elicit rapid and pronounced improvement in neuropathology and cognitive function in mouse models of Alzheimer's Disease (AD).

Recent research has implicated dysregulation of metal ions in the brain, particularly copper and zinc, in the pathogenesis of AD and the damaging accumulation of amyloid beta (Aβ) protein that is characteristic of this devastating disease. The ionophore clioquinol (CQ), an 8-hydroxyquinoline, has been shown to increase intracellular copper and zinc levels and decrease Aβ levels in cultured cells and in the brains of transgenic (Tg) AD mice. However, further studies in mice and humans demonstrated that brain entry of CQ was quite limited.

This research is published by Cell Press in the July 10th issue of the journal Neuron.

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Scientists unravel Leukaemia link

Scientists have unravelled the structure of a cell signalling receptor in the blood control system which when damaged is responsible for diseases such as leukaemia. Their discovery helps to explain, for the first time, how this receptor is activated and will form the springboard for the development of new treatments.

The findings, published on 8 August in the prestigious science journal, Cell, are the result of an interstate collaboration between a team of scientists led by Professor Michael Parker, St Vincent’s Institute (SVI), Melbourne and Professor Angel Lopez, Hanson Institute at the Institute of Medical and Veterinary Science, Adelaide.

Using leading edge technology that allows scientists to view minute parts of cells, the scientists have developed the first 3D image of the receptor’s structure and will use the unique knowledge it provides to find drugs to modify its action and control diseases such as Leukaemia and asthma.

Professor Lopez said: “Leukaemia is a type of cancer where an excessive number of malfunctioning white blood cells are produced. We have established the structure of a receptor that controls the actions of a blood-forming regulator called GM-CSF.”

He continued: “GM-CSF has been of interest to researchers and clinicians for many years now because its ‘controller’ or ‘receptor’, found on the surface of blood cells, is critical in regulating their many functions. In leukaemia some of the signals coming from the “receptor” are abnormal causing the blood cells to grow uncontrollably, malfunction or dangerously persist past their use-by-date.”

Professor Parker said: “Because our discovery shows precisely what the receptor looks like and also how it works, we can now begin to design new drugs to rein in the deadly abnormal blood cells. At the moment many leukaemias are treated with chemotherapy that destroys the diseased blood cells and bone marrow as well as normal cells. We hope that this discovery will lead to targeted therapies, more specific to the malfunctioning cells seen in diseases such as leukaemia.”

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Research Exposes New Target For Malaria Drugs

The malaria parasite has waged a successful guerrilla war against the human immune system for eons, but a study in this week's Journal of Biological Chemistry has exposed one of the tricks malaria uses to hide from the immune proteins, which may aid in future drug development. Malaria parasites (plasmodia) are transmitted to people via infected mosquitoes. Once inside their human hosts the parasites first set up shop in liver cells, then move into red blood cells (RBCs) to replicate and wait for the next mosquito to help continue the cycle. After plasmodia infect a blood cell, they send out clusters of sticky proteins to the cell surface, enabling them to attach to blood vessels and escape destruction by the host's spleen while they replicate. This tactic can be especially problematic during pregnancy as malaria-infected RBCs congregate in the vessel-rich placenta (the source of food and oxygen for the growing fetus), creating health problems such as anemia, low birth-weight, fever and more.

Targeting these sticky proteins with drugs is difficult, however, as plasmodia contain many different varieties, which they use to evade the human immune system. However, certain parts of the protein have to remain constant for proper function, and in this study, Matthew Higgins generated high-resolution 3-D structures of a malarial sticky protein that binds to placenta, PfEMP1, to detail how plasmodia protect these conserved areas. Higgins found that a variable region of PfEMP1 covers a section that is important for docking up with the placental wall. When the infected RBC gets close to chondroitin sulphate, a structural molecule on blood vessels, the variable region moves aside and ever so briefly exposes the binding region, just enough to allow anchoring to take place. Higgins notes that women in regions where malaria is endemic do gain some immunity to the build-up of RBCs at the placenta after multiple pregnancies by developing an immune response for PfEMP1. Targeting this conserved binding domain of the protein with pharmaceuticals that mimic chondroitin sulphate and expose this region might be an approach to hasten this immunity.

The Structure of a Chondroitin Sulfate-binding Domain Important in Placental Malaria.

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Certain HIV treatment less effective when used with anti-TB therapy

Combination antiretroviral therapy (ART) is frequently initiated in resource-limited countries when patients are being treated for tuberculosis. Co-administration of ART and anti-tubercular therapy may be complicated by shared toxicity or adverse drug interactions, according to background information in the article. Rifampicin-based anti-tubercular therapy reduces the plasma concentrations of the antiretroviral agents efavirenz and nevirapine. The virological consequences of these interactions are not well known.

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Novel therapies for age-related diseases such as Alzheimer's and Parkinson's

In their current study, published in the online edition of the journal Nature, Conboy and her team found that old muscle produces elevated levels of a molecule called TGF-beta, which is known to inhibit muscle growth. The researchers then showed that the muscle-deteriorating effects of TGF-beta can be reversed by blocking its pathway in old mice.

In the experiments, the researchers used RNA interference, which can silence specific genes, to inhibit the molecules that act downstream of TGF-beta to prevent cells from multiplying. They then locally injured the muscles of treated mice, as well as untreated old and young mice, by injecting a small amount of snake venom, which killed muscle tissue in the immediate vicinity.

After five days, the team found that the young mice were able to produce healthy cells to replace damaged tissue. The treated older mice, whose inhibitory pathways were suppressed, were able to regenerate new cells in much the same way. Not surprisingly, old untreated mice did not recover as well and developed fibroblasts and scar tissue around the injured site.

Researchers create molecule that nudges nerve stem cells to mature

The last time i blogged on stem cells it was rather about a challenge in Fresh hurdle for stem cell hunt, but this time its more on a positive note and fairly quite an interesting and welcome news... a SERENDIPITY!

Inspired by a chance discovery during another experiment, researchers at UT Southwestern Medical Center have created a small molecule that stimulates nerve stem cells to begin maturing into nerve cells in culture.

"This provides a critical starting point for neuro-regenerative medicine and brain cancer chemotherapy," said Dr. Jenny Hsieh, assistant professor of molecular biology and senior author of the paper, Small-molecule activation of neuronal cell fate, Jay W Schneider, Zhengliang Gao, Shijie Li, Midhat Farooqi, Tie-Shan Tang, Ilya Bezprozvanny, Doug E Frantz, Jenny Hsieh
SUMMARY: We probed an epigenetic regulatory path from small molecule to neuronal gene activation. Isoxazole small molecules triggered robust neuronal differentiation in adult neural stem.
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Fresh hurdle for stem cell hunt

Previously blogging on the topic of regenerative medicine in Regenerative Medicine Start-Up Created out of ORNL. A Nobel Prize-winning scientist says it could be tougher than first thought to harness the healing power of stem cells in medicine.

It had been hoped a single "master" cell could potentially be used to repair all damage in a single organ. Stem cells may be more varied than previously thought. Professor Mario Capecchi, from the University of Utah, found surprising clues that different stem cells might be working together in the same organ. This means experimental treatments relying on the wrong type might fail.

Professor Capecchi, writing in the Nature Genetics, said the finding suggested stem cell biology could be "more complicated" than previously thought, which could be bad news for patients hoping for the swift arrival of new therapies.

Bmi1 plays an essential part in the self-renewal of hematopoietic and neural stem cells. To investigate its role in other adult stem cell populations, we generated a mouse expressing a tamoxifen-inducible Cre from the Bmi1 locus. We found that Bmi1 is expressed in discrete cells located near the bottom of crypts in the small intestine, predominantly four cells above the base of the crypt (+4 position). Over time, these cells proliferate, expand, self-renew and give rise to all the differentiated cell lineages of the small intestine epithelium. The induction of a stable form of -catenin in these cells was sufficient to rapidly generate adenomas. Moreover, ablation of Bmi1⁺ cells using a Rosa26 conditional allele, expressing diphtheria toxin, led to crypt loss. These experiments identify Bmi1 as an intestinal stem cell marker in vivo. Unexpectedly, the distribution of Bmi1-expressing stem cells along the length of the small intestine suggested that mammals use more than one molecularly distinguishable adult stem cell subpopulation to maintain organ homeostasis.

Do you want to know more? Nature Genetics Published online: 8 June 2008

Regenerative Medicine Start-Up Created out of ORNL

Battelle Ventures has spun out a firm from the U.S. Department of Energy’s Oak Ridge National Laboratory (ORNL), with an initial $1.5 million seed investment. The company, called NellOne Therapeutics, will develop regenerative medicines. The funding will be tranched based on key technical milestones.

Towards a "holy grail" in human medicine: the ability to restore organs damaged through trauma, disease, cancer, or even the normal aging process.

Tissue or organ repair has been the ultimate goal of surgery from ancient times to the present day. Clearly, there is a lot of interest in the regeneration of tissues, and tissue repair in organisms is within reach. However, we are a long way from understanding how to coax the human body into regenerating complex body parts after injury or disease. As an example, regeneration of amputated limbs in amphibians - “epimorphic” regeneration which includes cellular dedifferentiation in the injured tissues of the limb stump and proliferation of these cells to form a distal blastema which undergoes patterning and growth to restore the missing limb structures. Some of the processes that are relatively little known and most of scientists are keen in understanding are:

• Processes involving cell recruitment of progenitor cells to the site of disease or injury and tissue-specific differentiation
• Growth factors and cytokines responsible for activating the body's own native cells to initiate regeneration
• Integration of the regenerated tissue within the surrounding host tissue and true differentiation through pathways involved in embryonic development
• Regulation of expression of a target gene can induce the expression of one or more tissue-inductive factors
• Direct the differentiation of stem or progenitor cells, or remove a factor that inhibits regeneration
• Ability of differentiating cells of muscle and other tissues to lose their ability to revert to the proliferative state and contribute to organ regeneration

Molecular Connections Private Ltd. Bangalore India has come up with its new Knowledgebase of all activating and inhibitory cell surface receptors and their complexes with the ligand(s) determined to date - Receptome:

• Knowledgebase, is a result of manually mining thousands of papers, on functional ligand-receptor pairs with their role & biological significance in developmental biology, as reported in literature till date
• Careful description of cell surface receptors, ligand(s) and molecular pathways integrated into complex networks and their expression patterns (signatures) involved in tissue regeneration
• Completely deciphered pathways of endogenous growth factors and cytokines and their receptors with their regulatory mechanisms involved in tissue regeneration
• Endogenous modulators or regulators of developmental ligand-receptor(s) widely studied in differentiation of stem or progenitor cells or tissue regeneration
• A platform to identify and track stem cells in different culture programmes using expression profiles of markers
• Comprehensive overview of the synergistic and combinatorial effects of receptors in tissue regeneration

X-men The man who grew a finger!

SiFi's alway feature and fantasize sprays and powders that can instantaneously close wounds catalyzing then and there the process of tissue regeneration. Every time you watch
Hugh Jackman as Wolverine regenerate and heals his wounds, wonder how?

How? Well that's the truly remarkable part. It wasn't a transplant. Mr Spievak re-grew his finger tip. He used a powder - or pixie dust as he sometimes refers to it while telling his story.

Mr Speivak's brother Alan - who was working in the field of regenerative medicine - sent him the powder.

For ten days Mr Spievak put a little on his finger.

"The second time I put it on I already could see growth. Each day it was up further. Finally it closed up and was a finger.

"It took about four weeks before it was sealed."

Now he says he has "complete feeling, complete movement."

The "pixie dust" comes from the University of Pittsburgh, though in the lab Dr Stephen Badylak prefers to call it extra cellular matrix.

"I think that within ten years that we will have strategies that will re-grow the bones, and promote the growth of functional tissue around those bones" Says Dr Stephen Badylak University of Pittsburgh

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Drug Target For The Most Potent Botulinum Neurotoxin Determined

Brookhaven Lab researchers Subramanyam Swaminathan, Desigan Kumaran and Richa Rawat.

"We have found a highly efficient inhibitor of botulinum neurotoxin type A - the most potent of seven neurotoxins produced by the bacterium Clostridium botulinum. This finding can lead to a very effective drug to stop the devastating effects of the toxin," said Dr. Subramanyam Swaminathan,

Botulinum neurotoxin -- responsible for the deadly food poisoning disease botulism and for the beneficial effects of smoothing out facial wrinkles - can also be used as a dreaded biological weapon. When ingested or inhaled, less than a billionth of an ounce can cause muscle paralysis and eventual death. Although experimental vaccines administered prior to exposure can inhibit the destructive action of this neurotoxin - the most deadly protein known to humans -- no effective pharmacological treatment exists. Scientists have now taken the first step toward designing an effective antidote to the most potent form of botulinum neurotoxin.

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British Team Finds Two Genes For Osteoporosis

British researchers have identified two common genetic mutations that increase the risk of osteoporosis and related bone fractures, according to a study released on Tuesday. These changes were present in 20 percent of the people studied and highlight the potential role of screening for the bone-thinning.

Talking about Osteoporosis, other related bone diseases affecting bone formation and repair. There has been increased interest both in academia and industry in tissue regeneration and working towards understanding the biological processes involved in self regeneration.

The key to success is in understanding basic developmental processes focused on tissue regeneration (including bone formation and repair). One such key resource researchers might be interested in, is Receptome – a knowledgebase of functional endogenous ligand-receptor pairs in developmental processes.

Few key applications areas are : to identify major mediators, roles in cellular processes, expression and role of specific cell surface receptors, multi-receptor pharmacology, identify high affinity ligands and activators, natural modulators of functional ligand-receptor pairs, critical signaling nodes, transcription factors, target genes, etc.

Tissue-specific blood stem cell line established from embryonic stem cells

A research team at the Umeå Center for Molecular Medicine (UCMM) in Sweden, led by Professor Leif Carlsson, has managed to specifically establish and isolate the tissue-specific stem cell that produces blood cells (blood stem cell) by using genetically modified embryonic stem cells.

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Nature News catches up on the state of gene therapy trials against blindness

Blogging already on the recent developments in Gene Therapy , This weekend two teams reported success in helping people to see again. Nature News catches up on the state of gene therapy trials against blindness due to Leber’s congenital amaurosis (LCA).

LCA, a rare inherited form of blindness. Patients with LCA have a genetic defect that affects the development of the light receptors in their eyes; typically they have poor vision at birth and are blind within three decades. Some 3,000 people are thought to be affected in the United States.

here are answers to some important questions that may arise like:

What sort of blindness do the new reports address?

Were the patients 'cured'?

How does it work?

What other treatments are being investigated for severe blindness?

Has gene therapy been trialled for blindness before?

for answers read

Beating heart tissue grown in lab

Talking about novel receptor genes expressed in human tissues. This morning's news featured, An international team of cell biologists has created heart tissue — complete with beat — in a test tube. The tissue culture contains three distinct cell types, each of which is important in functioning hearts, and is thus a step towards the advent of lab-grown heart-tissue transplants.

To day, research is considerably accelerated by the use of scientific knowledgebase and informatics tools which aid researchers significantly minimize time and effort spent on knowledge transfer across their teams and in scientific study. Thanks to such tools which supplement lab work and act as comprehensive repertoire that make optimal use of the plethora of data available in literature and centralize it as a searchable tool to investigate the characteristics of functional ligand-receptor pairs and their potential use and applications.

The research team led by Gordon Keller of the McEwen Centre for Regenerative Medicine in Toronto, Canada, created the heart cells from human embryonic stem cells. Researchers found that treating the embryonic stem cells with growth factors encourage them to develop into cardiovascular progenitor cells which have the potential to become any of three specialized types of heart cell — two muscle cell types (cardiomyocytes and vascular smooth muscle) and endothelial cells.

When these progenitor cells were grown in a dish, they developed their own intrinsic 'heartbeat'. What's more, when researchers transplanted a mixture of the three cell types into the hearts of mice with simulated heart disease, their heart function improved significantly. Although not yet tested in humans, the technique could offer a useful way to patch up heart muscle damaged by a heart attack.

Gene therapy success 'reverses' blindness

Experimental gene therapy trials have improved the vision of four people who suffer from hereditary blindness.

The preliminary results of two independent studies suggest that "repair" genes delivered to the eye might one day cure Leber congenital amaurosis (LCA), a rare disease that strikes about 1 in 80,000 people in the UK, and 2,000 Americans in total.

Equally important, say researchers, the treatments proved safe in the six patients who received the genes – delivered by a disabled virus – via eye surgery.

"This is really an exciting result for gene therapy as a field," says Katherine High, of the University of Pennsylvania Medical School in Philadelphia, who was part of an international team that presented the findings at a conference yesterday.

Another team led by Robin Ali, of University College London, presented similar results.

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Gene Therapy CMC Guidance Released

The US Food and Drug Administration issued a final guidance last week regarding investigational new drug applications for human gene therapy. Although gene therapy is still in the developmental stages, there is much hope for gene-based treatment and products. Because the therapy involves replacing a patient's faulty genetic material with normal genetic material,there is concern about safety in making sure replacement cells continue to function as they should. The guidance, therefore, focuses on the type of information that scientists need to consider and include in their documentation when studying these drugs and submitting them for FDA approval.

Based on a draft guidance that was issued in November 2004 (69 FR 64958), the final document, Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs), provides information on what to include in an original IND. The document also applies to combination products that contain a human gene therapy biological product in combination with a drug or device as part of the final product.

The full guidance is available for review and comment here.